Mutations in the Staphylococcus aureus Global Regulator CodY confer tolerance to an interspecies redox-active antimicrobial.

IF 4 2区 生物学 Q1 GENETICS & HEREDITY
PLoS Genetics Pub Date : 2025-03-07 eCollection Date: 2025-03-01 DOI:10.1371/journal.pgen.1011610
Anthony M Martini, Sara A Alexander, Anupama Khare
{"title":"Mutations in the Staphylococcus aureus Global Regulator CodY confer tolerance to an interspecies redox-active antimicrobial.","authors":"Anthony M Martini, Sara A Alexander, Anupama Khare","doi":"10.1371/journal.pgen.1011610","DOIUrl":null,"url":null,"abstract":"<p><p>Bacteria often exist in multispecies communities where interactions among different species can modify individual fitness and behavior. Although many competitive interactions have been described, molecular adaptations that can counter this antagonism and preserve or increase fitness remain underexplored. Here, we characterize the adaptation of Staphylococcus aureus to pyocyanin, a redox-active interspecies antimicrobial produced by Pseudomonas aeruginosa, a co-infecting pathogen frequently isolated from wound and chronic lung infections with S. aureus. Using experimental evolution, we identified mutations in a conserved global transcriptional regulator, CodY, that confer tolerance to pyocyanin and thereby enhance survival of S. aureus. A pyocyanin tolerant CodY mutant also had a survival advantage in co-culture with P. aeruginosa, likely through tolerance specifically to pyocyanin. The transcriptional response of the CodY mutant to pyocyanin indicated a two-pronged defensive response compared to the wild type. First, the CodY mutant strongly suppressed metabolism by downregulating core metabolic pathways , especially translation-associated genes, upon exposure to pyocyanin. Metabolic suppression via ATP depletion was sufficient to provide comparable protection against pyocyanin to the wild-type strain. Second, while both the wild-type and CodY mutant strains upregulated oxidative stress response pathways upon pyocyanin exposure, the CodY mutant overexpressed multiple stress response genes compared to the wild type. We determined that catalase overexpression was critical to pyocyanin tolerance as its absence eliminated tolerance in the CodY mutant and overexpression of catalase was sufficient to impart tolerance to the wild-type strain against purified pyocyanin and in co-culture with WT P. aeruginosa. Together, these results suggest that both transcriptional responses of reduced metabolism and an increased oxidative stress response likely contribute to pyocyanin tolerance in the CodY mutant. Our data thus provide new mechanistic insight into adaptation toward interbacterial antagonism via altered regulation that facilitates multifaceted protective cellular responses.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 3","pages":"e1011610"},"PeriodicalIF":4.0000,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11918324/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"PLoS Genetics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1371/journal.pgen.1011610","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/3/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0

Abstract

Bacteria often exist in multispecies communities where interactions among different species can modify individual fitness and behavior. Although many competitive interactions have been described, molecular adaptations that can counter this antagonism and preserve or increase fitness remain underexplored. Here, we characterize the adaptation of Staphylococcus aureus to pyocyanin, a redox-active interspecies antimicrobial produced by Pseudomonas aeruginosa, a co-infecting pathogen frequently isolated from wound and chronic lung infections with S. aureus. Using experimental evolution, we identified mutations in a conserved global transcriptional regulator, CodY, that confer tolerance to pyocyanin and thereby enhance survival of S. aureus. A pyocyanin tolerant CodY mutant also had a survival advantage in co-culture with P. aeruginosa, likely through tolerance specifically to pyocyanin. The transcriptional response of the CodY mutant to pyocyanin indicated a two-pronged defensive response compared to the wild type. First, the CodY mutant strongly suppressed metabolism by downregulating core metabolic pathways , especially translation-associated genes, upon exposure to pyocyanin. Metabolic suppression via ATP depletion was sufficient to provide comparable protection against pyocyanin to the wild-type strain. Second, while both the wild-type and CodY mutant strains upregulated oxidative stress response pathways upon pyocyanin exposure, the CodY mutant overexpressed multiple stress response genes compared to the wild type. We determined that catalase overexpression was critical to pyocyanin tolerance as its absence eliminated tolerance in the CodY mutant and overexpression of catalase was sufficient to impart tolerance to the wild-type strain against purified pyocyanin and in co-culture with WT P. aeruginosa. Together, these results suggest that both transcriptional responses of reduced metabolism and an increased oxidative stress response likely contribute to pyocyanin tolerance in the CodY mutant. Our data thus provide new mechanistic insight into adaptation toward interbacterial antagonism via altered regulation that facilitates multifaceted protective cellular responses.

金黄色葡萄球菌全球调节因子CodY的突变赋予对种间氧化还原活性抗菌素的耐受性。
细菌通常存在于多物种群落中,不同物种之间的相互作用可以改变个体的适应性和行为。尽管已经描述了许多竞争性相互作用,但能够对抗这种对抗并保持或增加适应性的分子适应仍未得到充分探索。在这里,我们描述了金黄色葡萄球菌对pyocyanin的适应性,pyocyanin是一种由铜绿假单胞菌产生的氧化还原活性的种间抗菌剂,是一种经常从伤口和慢性肺部感染的金黄色葡萄球菌中分离出来的共感染病原体。通过实验进化,我们确定了保守的全局转录调节因子CodY的突变,该突变赋予了对pyocyanin的耐受性,从而提高了金黄色葡萄球菌的存活率。耐pyocyanin的CodY突变体在与铜绿假单胞菌共培养时也具有生存优势,可能是通过对pyocyanin的特异性耐受性。与野生型相比,CodY突变体对花青素的转录反应显示出双管齐下的防御反应。首先,CodY突变体在暴露于花青素后,通过下调与核心代谢相关的途径,特别是翻译相关的基因,强烈抑制代谢。通过ATP消耗的代谢抑制足以提供与野生型菌株相当的对pyocyanin的保护。其次,尽管野生型和CodY突变菌株在暴露于花色素苷后都上调了氧化应激反应途径,但与野生型相比,CodY突变菌株过度表达了多个应激反应基因。我们确定过氧化氢酶的过表达对pyocyanin耐受性至关重要,因为在CodY突变体中过氧化氢酶的缺失消除了耐受性,而过氧化氢酶的过表达足以使野生型菌株对纯化的pyocyanin产生耐受性,并与WT P. aeruginosa共培养。总之,这些结果表明,代谢减少的转录反应和氧化应激反应的增加可能有助于CodY突变体的pyocyanin耐受性。因此,我们的数据为通过改变调节促进多方面保护性细胞反应来适应细菌间拮抗提供了新的机制见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
PLoS Genetics
PLoS Genetics GENETICS & HEREDITY-
自引率
2.20%
发文量
438
期刊介绍: PLOS Genetics is run by an international Editorial Board, headed by the Editors-in-Chief, Greg Barsh (HudsonAlpha Institute of Biotechnology, and Stanford University School of Medicine) and Greg Copenhaver (The University of North Carolina at Chapel Hill). Articles published in PLOS Genetics are archived in PubMed Central and cited in PubMed.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信